MV130: Efficacy and Safety Evaluation in Recurrent Wheezing Attacks

• Sponsor: Inmunotek S.L. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01734811
• Collaborator: Unidad de Investigacion Medica en Epidemiologia Clinica (Other)
• Enrollment: 120
• Locations: 2
• Arms: 2
• Duration (Months): 52
• Patients Per Site: 60
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The study will be conducted in two hospitals of the same geographic area. It will be included children <3-years-old with recurrent wheezing attacks, confirmed by the review of the medical records, in the previous 12 months or a shorter time for those younger than one year.

Condition or Disease	Intervention/Treatment	Phase
Bronchospasm; Bronchiolitis; Bronchospasm; Bronchitis	Biological: Biological vaccine	Phase 3

Detailed Description

This randomized, double-blind, placebo-controlled, parallel-group study will included 120 children <3 years old with ≥3 episodes of wheezing during the previous year. They will receive active treatment or placebo for six months. The main outcome will be the number of wheezing attacks during one year. Other outcomes were duration and severity of wheezing attacks , symptom and medication scores, and use of health resources.

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, placebo-controlled, multi centre, parallel-group studyRandomized, double-blind, placebo-controlled, multi centre, parallel-group study
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Randomized Double-blind Placebo-controlled, Parallel, Multi Centre Clinical Trial of Sublingual Bacterial Vaccine in Children With Recurrent Bronchospasm (Wheezing Attacks) for the Evaluation of Efficacy, Security and Clinical Impact.
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation	Biological: Biological vaccine; daily spray (2 puff of 100 µL) for six months
Experimental: Biological vaccine The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation	Biological: Biological vaccine; daily spray (2 puff of 100 µL) for six months

Outcome Measures

Primary Outcome Measures

1. Number of Recurrent Bronchospasm (Wheezing Attacks) [12 months]

   Assessment of reduction of bronchospasm (wheezing attacks) episodes at 12 months. The number of bronchospasm (wheezing attacks) episodes, in active and placebo group will be compared

Secondary Outcome Measures

1. Duration (Days) of Wheezing Attacks (WA) [12 months]

   Review of bronchospasm (wheezing attacks) duration per patient

2. Time Until Appearance of First WA [12 months]

   time (days) until appearance of first wheezing attack (WA)

3. Number of Days With Wheezing Attacks During the Study [12 months]

   Review of the number of days with wheezing attacks during the study

4. Number of Patients With Recurrent WA During the Study [12 months]

   Review of number of patients with recurrent WA during the whole study

5. Symptom Score During Wheezing Attacks [12 months]

   Total of Symptom score during wheezing attacks. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed. Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3. The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC. The total symptom score was calculated as the sum of all individual scores during the wheezing attacks.

6. Medication Score During WA [12 months]

   Review of medication consumption during wheezing attacks. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed. Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded. The total symptom score was calculated as the sum of all individual scores during the wheezing attacks.

7. Overall Symptom Score [12 months]

   Review of symptoms during the whole study. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed. Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3. The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC. The total symptom score was calculated as the sum of all individual scores during the whole study

8. Overall Medication Score [12 months]

   Review of medication consumption during the whole study. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed. Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded. The total symptom score was calculated as the sum of all individual scores during the whole study.

Other Outcome Measures

1. Use of Health and Social Resources During the Whole Period of the Study. [12 months]

   The use of health and social resources during the study was also recorded: days of hospitalization in ward and/or intensive care unit, visits to the emergency units, unscheduled visits to the pediatrician and/or to the specialist, telephone calls to the pediatrician, complementary tests (chest radiogram, blood analysis, others), days of school absenteeism and caregiver-days when the children needed them. The data were obtained from the diary cards and confirmed through the review of medical records. Maximum value corresponds to the maximum days spent in health resources (specified above) and the minimum value corresponds to the minimum of days spent in health resources (specified above)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 36 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects whose parents /legal representative have given written informed consent.

• Both gender

• Subject up to 36 months of age.

• Subjects with recurrent bronchospasms (wheezing attacks); 3 or more exacerbations in the last 12 months

Exclusion Criteria:

• Subjects whose parents/legal representative have not given written informed consent.

• Subjects out of aged range

• Subjects with malignancies or chemotherapy treatment

• Subjects included in another clinical trial in the last 12 months.

• Subject in immunosuppressive or immunostimulatory treatment

• Subjects who have received iv gamma globulin in the past 12 months.

• Subjects diagnosed with candidiasis or fungal recurrent infections.

• Subjects diagnosed with malabsorption syndrome

• Subjects with clinical allergy to common aeroallergens in the geographical area.

• Subjects with hepatitis virus infections, HIV and tuberculosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital de Manises	Manises	Valencia	Spain	46940
2	Hospital Universitario y Politécnico La Fe	Valencia		Spain	46026

Sponsors and Collaborators

• Inmunotek S.L.
• Unidad de Investigacion Medica en Epidemiologia Clinica

Investigators

• Study Director: Miguel Casanovas, PhD; MD,

Study Documents (Full-Text)

None provided.

More Information

Publications

• Alecsandru D, Valor L, Sánchez-Ramón S, Gil J, Carbone J, Navarro J, Rodríguez J, Rodríguez-Sainz C, Fernández-Cruz E. Sublingual therapeutic immunization with a polyvalent bacterial preparation in patients with recurrent respiratory infections: immunomodulatory effect on antigen-specific memory CD4+ T cells and impact on clinical outcome. Clin Exp Immunol. 2011 Apr;164(1):100-7. doi: 10.1111/j.1365-2249.2011.04320.x.

• Responsible Party: Inmunotek S.L.
• ClinicalTrials.gov Identifier: NCT01734811
• Other Study ID Numbers: MV130-SLG-002; 2012-002450-24
• First Posted: Nov 28, 2012
• Last Update Posted: Nov 8, 2021
• Last Verified: Oct 1, 2020

• Keywords provided by Inmunotek S.L.: Vaccine; Bronchospasm
• Additional relevant MeSH terms: Bronchiolitis; Bronchitis; Bronchial Spasm; Respiratory Sounds

Study Results

Participant Flow

Recruitment Details	October 2012 - May 2015 subjects enrollment. 120 children <3 years old with recurrent WA, defined as 3 or more episodes of WA during the previous year. . WA were confirmed by the review of the medical records. Aeroallergen sensitization at baseline was used as an exclusion criterion to avoid an eventual WA due to allergic asthma.

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Period Title: Overall Study
STARTED	58	62
COMPLETED	54	59
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Placebo	Biological Vaccine	Total
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	Total of all reporting groups
Overall Participants	58	62	120
Age (Count of Participants)
<=18 years	58 100%	62 100%	120 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	23 (8)	23 (7)	23 (8)
Sex: Female, Male (Count of Participants)
Female	26 44.8%	25 40.3%	51 42.5%
Male	32 55.2%	37 59.7%	69 57.5%
Region of Enrollment (participants) [Number]
Spain	58 100%	62 100%	120 100%

Outcome Measures

1. Primary Outcome

Title	Number of Recurrent Bronchospasm (Wheezing Attacks)
Description	Assessment of reduction of bronchospasm (wheezing attacks) episodes at 12 months. The number of bronchospasm (wheezing attacks) episodes, in active and placebo group will be compared
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Number [events]	299	176

2. Secondary Outcome

Title	Duration (Days) of Wheezing Attacks (WA)
Description	Review of bronchospasm (wheezing attacks) duration per patient
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Median (Inter-Quartile Range) [days]	7.9	6.0

3. Secondary Outcome

Title	Time Until Appearance of First WA
Description	time (days) until appearance of first wheezing attack (WA)
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Median (Inter-Quartile Range) [days]	5.0	41.0

4. Secondary Outcome

Title	Number of Days With Wheezing Attacks During the Study
Description	Review of the number of days with wheezing attacks during the study
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Median (Inter-Quartile Range) [days]	42.0	19.2

5. Secondary Outcome

Title	Number of Patients With Recurrent WA During the Study
Description	Review of number of patients with recurrent WA during the whole study
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Count of Participants [Participants]	45 77.6%	36 58.1%

6. Secondary Outcome

Title	Symptom Score During Wheezing Attacks
Description	Total of Symptom score during wheezing attacks. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed. Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3. The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC. The total symptom score was calculated as the sum of all individual scores during the wheezing attacks.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Median (Inter-Quartile Range) [units on a scale]	155.0	80.0

7. Secondary Outcome

Title	Medication Score During WA
Description	Review of medication consumption during wheezing attacks. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed. Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded. The total symptom score was calculated as the sum of all individual scores during the wheezing attacks.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Median (Inter-Quartile Range) [units on a scale]	424.0	164.0

8. Secondary Outcome

Title	Overall Symptom Score
Description	Review of symptoms during the whole study. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed. Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3. The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC. The total symptom score was calculated as the sum of all individual scores during the whole study
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Median (Inter-Quartile Range) [units on a scale]	421.0	276.5

9. Secondary Outcome

Title	Overall Medication Score
Description	Review of medication consumption during the whole study. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed. Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded. The total symptom score was calculated as the sum of all individual scores during the whole study.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Median (Inter-Quartile Range) [units on a scale]	1043.5	618.5

10. Other Pre-specified Outcome

Title	Use of Health and Social Resources During the Whole Period of the Study.
Description	The use of health and social resources during the study was also recorded: days of hospitalization in ward and/or intensive care unit, visits to the emergency units, unscheduled visits to the pediatrician and/or to the specialist, telephone calls to the pediatrician, complementary tests (chest radiogram, blood analysis, others), days of school absenteeism and caregiver-days when the children needed them. The data were obtained from the diary cards and confirmed through the review of medical records. Maximum value corresponds to the maximum days spent in health resources (specified above) and the minimum value corresponds to the minimum of days spent in health resources (specified above)
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months	The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
Measure Participants	58	62
Median (Inter-Quartile Range) [days]	14.5	11.0

Adverse Events

Time Frame	Up to 12 months.
Adverse Event Reporting Description	Adverse Events were registered throughout the trial. Grading was according to EAACI guidelines.
Arm/Group Title	Placebo		Biological Vaccine
Arm/Group Description	The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months		The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation Biological vaccine: daily spray (2 puff of 100 µL) for six months
All Cause Mortality
	Placebo		Biological Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/62 (0%)
Serious Adverse Events
	Placebo		Biological Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/58 (1.7%)		0/62 (0%)
Nervous system disorders
Epilectic seizure	1/58 (1.7%)	1	1/62 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Biological Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/62 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.